Is MET p.Arg191Trp (c.571C>T) pathogenic?

MET p.Arg191Trp (c.571C>T) is classified Likely benign in MET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.2524); Very rare (popmax 0.00534%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Arg191Trp (c.571C>T)?

MET p.Arg191Trp (c.571C>T) is associated with hereditary neoplastic syndrome, renal cell carcinoma (ClinVar).

How common is MET p.Arg191Trp (c.571C>T) in the general population?

MET p.Arg191Trp (c.571C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about MET p.Arg191Trp (c.571C>T)?

AlphaMissense predicts likely benign (score 0.2524) — an in-silico prediction, not a clinical call.

MET p.Arg191Trp

c.571C>T · rs530932258 · VCV568557

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2524 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2524	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -9.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP -3.7, phastCons 0.033
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,880 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000496% 8/1,613,804 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,720
European (non-Finnish)	0.000339%	294,993

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MET
Protein: p.Arg191Trp
Coding: c.571C>T
MANE Select: NM_000245
dbSNP: rs530932258
Type: single nucleotide variant
Location: chr7:116699655 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 191: the sema domain

Full MET gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal cell carcinoma

Similar variants

MET p.Arg191Gly Uncertain significance ★★ ⚠ same residue
MET p.Arg191= Benign/Likely benign ★★ same residue
MET p.Arg191Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Arg191Leu Uncertain significance ★ same residue
MET p.His1094Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
MET p.Met1131Thr Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1092Ile Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1220Ile Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/met-p-arg191trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown